Diabetic vascular disease (DVD) is a cause of significant morbidity in individuals with Type 2 diabetes. It is estimated that 50% of patients have already got vascular complications at the time of diagnosis with Type 2 diabetes. It is, therefore, important to develop techniques that may assist in early identifications of possible markers for vascular complications. Our work aims to identify proteins that can be used as biomarkers to diagnose DVD early in its development, thereby enabling earlier interventions to delay or halt its progression. We have recently discovered a novel non-destructive method of protein sampling, employing the polymer styrene maleic acid (SMA), to extract nanodiscs (containing membrane-bound proteins) from the membranes of cells without killing them. Our pilot data from liquid chromatography–mass spectrometry (LC-MS) based proteomics analysis of proteins isolated using SMA from intact rat aortic tissue ex vivo will be presented. We can show that we have recovered proteins from plasma membrane, intracellular membranes and cell cytosol without any associated cell death. This serves as proof-of-principle that SMA application is a promising method for non-destructively extracting proteins from vascular endothelial cells. Next, we applied SMA to the aortic tissue of a widely-used model of diabetes in genetically-modified (db/db) mice and their wild-type counterparts, to study the changes in the levels of expression of the SMA-recovered proteins in diabetic mice compared to wild-type mice over the course of early disease development. Preliminary data from our quantitative LC-MS proteomics analysis of samples from mouse aortic tissue will also be presented. We can show that we have successfully identified approximately 300 proteins isolated using our SMA-based method which demonstrates the feasibility of our approach. By understanding of the molecular changes during DVD development, this project aims to facilitate earlier detection of DVD and thus lead to earlier interventions for patients